follicular lymphoma
Recently Published Documents





Cureus ◽  
2022 ◽  
Hiroto Suzuki ◽  
Yasuhiko Hamada ◽  
Kyosuke Tanaka ◽  
Noriyuki Horiki ◽  
Hayato Nakagawa

Haematologica ◽  
2022 ◽  
Karoline Koch ◽  
Julia Richter ◽  
Christoph Hanel ◽  
Andreas Huttmann ◽  
Ulrich Duhrsen ◽  

The sole distinguishing feature of follicular lymphoma grade 3B and diffuse large B-cell lymphoma is the growth pattern assessed by histopathology analysis. Diffuse growth defines diffuse large B-cell lymphoma but the clinical relevance of this finding when occurring in follicular lymphoma grade 3B is uncertain. To address this question, individual and coexisting follicular lymphoma grade 3B and diffuse large B-cell lymphoma were separated and analyzed for immunophenotype and molecular genetic features by fluorescence in situ hybridization, targeted sequencing and gene expression profiling. Clinical features of follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma were studied in homogeneously treated patients from a prospective randomized trial. Follicular lymphoma grade 3B and diffuse large B-cell lymphoma frequently show intermediate growth pattern and/or occurred simultaneously in the same tissue at the time of initial diagnosis. When occurring simultaneously follicular lymphoma grade 3B and diffuse large B-cell lymphoma do not differ significantly in genetic aberrations or phenotype but distinct features in gene expression reflect divergent microenvironment. Follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma do not differ in major clinical parameters such as international prognostic index, response to immunochemotherapy, progression or overall survival. Follicular lymphoma grade 3B and simultaneous diffuse large B-cell lymphoma are molecularly homogenous. Histological detection of diffuse large B-cell lymphoma is not associated with features of a more aggressive disease and does not reflect transformation or progression of follicular lymphoma Grade 3B.

Loretta J. Nastoupil ◽  
Collin K Chin ◽  
Jason R Westin ◽  
Nathan H Fowler ◽  
Felipe Samaniego ◽  

PD-1 blockade enhances the function of anti-tumor T-cells and antibody-dependent cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 follicular lymphoma (FL) patients with rituximab-sensitive disease who relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200mg IV every 3 weeks for up to 16 cycles and rituximab was given at 375mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AE) were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), aseptic meningitis (3%) and pancreatitis (3%). Low-grade immune-related AEs were reported for 80% of patients, including diarrhea (43%), liver enzyme abnormalities (33%), thyroid dysfunction (27%), and rash (23%). Grade 3 or 4 immune related AEs occurred in 13% of patients. Treatment-related AEs led to discontinuation in 6 (20%) patients. Overall response rate (primary endpoint) was 67% and complete response rate was 50%. Median progression-free survival (PFS) was 12.6 months (95% CI, 8.2-27.6 months), the 3-year overall survival rate was 97%, and 23% of patients were in remission at a median follow up of 35 months. Presence of a high CD8+ T-effector score at baseline in the tumor was associated with induction of a complete response and improved PFS. In this single arm, phase 2 study, the combination of pembrolizumab and rituximab demonstrates favorable efficacy and safety profile in relapsed FL. This trial is registered at NCT02446457.

2022 ◽  
Vol 11 ◽  
Adrián Mosquera Orgueira ◽  
Miguel Cid López ◽  
Andrés Peleteiro Raíndo ◽  
Aitor Abuín Blanco ◽  
Jose Ángel Díaz Arias ◽  

Follicular Lymphoma (FL) has a 10-year mortality rate of 20%, and this is mostly related to lymphoma progression and transformation to higher grades. In the era of personalized medicine it has become increasingly important to provide patients with an optimal prediction about their expected outcomes. The objective of this work was to apply machine learning (ML) tools on gene expression data in order to create individualized predictions about survival in patients with FL. Using data from two different studies, we were able to create a model which achieved good prediction accuracies in both cohorts (c-indexes of 0.793 and 0.662 in the training and test sets). Integration of this model with m7-FLIPI and age rendered high prediction accuracies in the test set (cox c-index 0.79), and a simplified approach identified 4 groups with remarkably different outcomes in terms of survival. Importantly, one of the groups comprised 27.35% of patients and had a median survival of 4.64 years. In summary, we have created a gene expression-based individualized predictor of overall survival in FL that can improve the predictions of the m7-FLIPI score.

2022 ◽  
Cody A Ramirez ◽  
Felix Frenkel ◽  
Michelle Becker ◽  
Erica K Barnell ◽  
Ethan D McClain ◽  

Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that polyvalent vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole exome sequencing (WES) and RNA sequencing (RNA-Seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-Seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by alignment of B-cell receptor (BCR) CDR3 regions from RNA-Seq data, grouping at the protein level, and comparison to the BCR repertoire of RNA-Seq data from healthy individuals. An average of 52 somatic mutations per patient (range: 2-172) were identified, and two or more (median: 15) high-quality neoantigens were predicted for 56 of 58 samples. The predicted neoantigen peptides were composed of missense mutations (76%), indels (9%), gene fusions (3%), and BCR sequences (11%). Building off of these preclinical analyses, we initiated a pilot clinical trial using personalized neoantigen vaccination combined with PD-1 blockade in patients with relapsed or refractory FL (#NCT03121677). Synthetic long peptide (SLP) vaccines were successfully synthesized for and administered to all four patients enrolled to date. Initial results demonstrate feasibility, safety, and potential immunologic and clinical responses. Our study suggests that a genomics-driven personalized cancer vaccine strategy is feasible for patients with FL, and this may overcome prior challenges in the field.

Taku Tsukamoto ◽  
Yuichi Tokuda ◽  
Masakazu Nakano ◽  
Kei Tashiro ◽  
Junya Kuroda

Haematologica ◽  
2022 ◽  
Vol 107 (1) ◽  
pp. 19-34 ◽  
David Qualls ◽  
Gilles Salles

The management of patients with relapsed or refractory follicular lymphoma has evolved markedly in the last decade, with the availability of new classes of agents (phosphoinositide 3-kinase inhibitors, immunomodulators, epigenetic therapies, and chimeric antigen receptor T cells) supplementing the multiple approaches already available (cytotoxic agents, anti-CD20 antibodies, radiation therapy, radioimmunotherapy, and autologous and allogeneic transplants). The diversity of clinical scenarios, the flood of data derived from phase II studies, and the lack of randomized studies comparing treatment strategies preclude firm recommendations and require personalized decisions. Patients with early progression require specific attention given the risk of histological transformation and their lower response to standard therapies. In sequencing therapies, one must consider prior treatment regimens and the potential need for future lines of therapy. Careful evaluation of risks and expected benefits of available options, which vary depending on location and socioeconomics, should be undertaken, and should incorporate the patient’s goals. Preserving quality of life for these patients is essential, given the likelihood of years to decades of survival and the possibility of multiple lines of therapy. The current landscape is likely to continue evolving rapidly with other effective agents emerging (notably bispecific antibodies and other targeted therapies), and multiple combinations being evaluated. It is hoped that new treatments under development will achieve longer progression-free intervals and minimize toxicity. A better understanding of disease biology and the mechanisms of these different agents should provide further insights to select the optimal therapy at each stage of disease.

2022 ◽  
Vol 12 (1) ◽  
Yucai Wang ◽  
Shouhao Zhou ◽  
Xinyue Qi ◽  
Fang Yang ◽  
Matthew J. Maurer ◽  

Abstract Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1–3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.

Haematologica ◽  
2022 ◽  
Vol 107 (1) ◽  
pp. 7-18 ◽  
Guillaume Cartron ◽  
Judith Trotman

Follicular lymphoma is a heterogeneous B-cell lymphoma both in presentation and at progression. For most patients it is a chronic, relapsing indolent disease with overall survival expectations now potentially beyond 20 years. However, in a significant minority (~20%) who experience early progression or histological transformation after treatment, the disease no longer has an indolent behavior. This review looks at the development of prognostic indices, staging and therapies for follicular lymphoma, identifying where the data can, and cannot, guide the multidisciplinary team to determine an individualized approach to first-line therapy. A nuanced patient- and disease-specific approach is necessary to maximize disease response and survival while minimizing therapeutic toxicity.

Sign in / Sign up

Export Citation Format

Share Document